Abstract：
The myelin sheath is an essential structure for the rapid transmission of electrical impulses through axons, and peripheral myelination is a well-programmed postnatal process of Schwann cells (SCs), the myelin-forming peripheral glia. SCs transdifferentiate into demyelinating SCs (DSCs) to remove the myelin sheath during Wallerian degeneration after axonal injury and demyelinating neuropathies, and macrophages are responsible for the degradation of myelin under both conditions. In this study, the mechanism by which DSCs acquire the ability of myelin exocytosis was investigated. Using serial ultrastructural evaluation, we found that autophagy-related gene 7-dependent formation of a \"secretory phagophore (SP)\" and tubular phagophore was necessary for exocytosis of large myelin chambers by DSCs. DSCs seemed to utilize myelin membranes for SP formation and employed p62/sequestosome-1 (p62) as an autophagy receptor for myelin excretion. In addition, the acquisition of the myelin exocytosis ability of DSCs was associated with the decrease in canonical autolysosomal flux and was demonstrated by p62 secretion. Finally, this SC demyelination mechanism appeared to also function in inflammatory demyelinating neuropathies. Our findings show a novel autophagy-mediated myelin clearance mechanism by DSCs in response to nerve damage.
摘要：
髓鞘是电脉冲通过轴突快速传递的重要结构，外周髓鞘形成是施万细胞（SCs）的良好编程的出生后过程，形成髓鞘的外周神经胶质。在轴突损伤和脱髓鞘性神经病后的Wallerian变性过程中，SCs转分化为脱髓鞘SCs（DSC）以去除髓鞘，和巨噬细胞在两种条件下都负责髓磷脂的降解。在这项研究中,研究了DSC获得髓鞘胞吐能力的机制。使用连续的超微结构评估，我们发现自噬相关基因7依赖性的“分泌型吞噬体（SP）”和管状吞噬体的形成是DSCs胞吐大髓鞘室所必需的。DSCs似乎利用髓磷脂膜进行SP形成，并采用p62/螯合体-1（p62）作为自噬受体进行髓磷脂排泄。此外,获得DSCs的髓鞘胞吐能力与经典自溶酶体通量的减少相关,并通过p62分泌得到证实.最后,这种SC脱髓鞘机制似乎也在炎性脱髓鞘性神经病中起作用。我们的发现显示了一种新型的自噬介导的神经损伤的DSCs的髓磷脂清除机制。
